The goal of this research project is to delineate the pathogenesis of the macular disease of presumed ocular histoplasmosis. An experimental animal model is required since inadequate histopathologic material is available from humans with this eye disease. During the previous granting period we have successfully established a sub-human primate model of ocular histoplasmosis resulting in multifocal histoplasmic choroiditis in the macular and nervehead area. These lesions spontaneously resolve over a period of weeks resulting in "atrophic spots" which are also characteristic of the human eye disease. The major goal of this renewal request is to further study the natural course of histoplasmic choroiditis in primates by serial fundus photography, fluorescein angiography, fungal cultures, and histopathology of enucleated eyes. We will be particularly interested in the histopathology of late natural course lesions, with emphasis on duration of lymphocytic foci and organisms in areas of choroiditis. In addition, serial sections will be prepared to assess damage or changes in Bruch's membrane and the retinal pigment epithelium. Attempts to reactivate clinically inactive atrophic choroidal foci will be carried out utilizing such techniques as repeated histoplasmin skin testing, intravascular challenge with histoplasma antigen, re-infection, non-specific stimulation of immune response using Concanavalin A and lipopolysacchride, and mechanical irritation of Bruch's membrane by photocoagulation. The role of inflamation and/or subretinal neovascularization in the development of such activation will be studied by serial fluorescein angiography, fundus photography, and histopathology. Ultimately, when models of reactivation have been established, trials of appropriate therapy will be considered.